The Legal test (acetoacetic acid and/or acetone and sodium nitroprusside in alkaline medium) was studied for interference with the uroprotective drug mesna and related compounds. All free- sulfhydryl compounds tested produced false-positive reactions in this test for ketones. The presence of acidic groups in the structure appeared to increase the nitroprusside reactivity of free sulfhydryl compounds, whereas the presence of an amino group appeared to decrease it. Procedures have been elaborated to recognize and rule out false-positive ketone reactions with these compounds in clinical specimens.